Inhibitory effect of glycyrrhizin on the phosphorylation and DNA-binding abilities of high mobility group proteins 1 and 2 in vitro.

The physiological correlation between glycyrrhizin (GL) and high mobility group proteins I and 2 (HMG1/2) and the inhibitory effect of GL on their phosphorylation by three protein kinases (CK-I, CK-II and PKC) were investigated biochemically in vitro. It was found that GL binds directly to HMG1/2, because (i) HMG1/2 have a high affinity with a GL-affinity column; and (ii) GL induces the conformational changes in HMG1/2. Both purified HMG1/2 functioned as phosphate acceptors for these two protein kinases (CK-I and PKC), but not phosphorylated by CK-II. Phosphorylation of HMG1/2 by two protein kinases (CK-I and PKC) was completely inhibited by a glycyrrhetinic acid derivative (oGA) at one-tenth the concentration of GL. Also, the DNA-binding abilities of HNG1/2 were reduced by GL in a dose-dependent manner. These results show that the binding of GL to HMG1/2 results in the inhibition of their physiological activities (DNA-binding ability and phosphorylation by PKC or CK-I) in vitro. The GL-induced inhibition of the physiological activities of HMG1/2 may be involved in the anti-inflammatory effect of GL in vivo.